PURPOSE AND PROGRAM CHARACTERISTICS: This proposal represents a continuation of a training program in the biochemistry of growth regulation and oncogenesis, now entering its twenty-fourth year. The training faculty is drawn from the UCSD Department of Chemistry and Biochemistry, from the Division of Biological Sciences, and from the School of Medicine. All members of the training faculty are also members of the Moores UCSD Cancer Center and participate in their programs. In this renewal, the training faculty has been strengthened by the addition of 14 outstanding faculty members, bringing the total number of faculty members to 32, including six members of the National Academy of Sciences. The training faculty is organized into four research areas focusing on: kinases, phosphatases, and their signaling pathways;the control of cell cycle progression, DNA checkpoints, and apoptosis;transcription factors and their signaling pathways;and the chemistry of cancer therapeutics. This program exhibits a unique emphasis on structural and molecular approaches. Training involves formal courses, journal clubs, annual symposia, and a variety of events to promote program cohesion and interaction. TRAINEES: Our current and past trainees have excellent records of research accomplishments. We have requested seven postdoctoral positions in Years 24 and 25, and increasing thereafter to reach ten postdoctoral trainees in Year 28. No change is requested in predoctoral slots. The requested slots are justified by the enormous expansion currently underway at UCSD in undergraduate and graduate enrollments, by the ability of the training faculty to recruit outstanding predoctoral and postdoctoral trainees to their labs, and by the highly interactive nature of the training labs that collectively provide a superb training environment. Predoctoral trainees will be drawn from graduate students accepted into the Department of Chemistry and Biochemistry and, with this renewal, from graduate students in Biological Sciences. Postdoctoral trainees will be selected from postdoctoral candidates applying for positions in the laboratories of the training faculty. All trainees accepted into our program are expected to have strong backgrounds in chemistry, biochemistry, and molecular and cell biology. PROGRAM CHANGES: This renewal highlights several changes to the program, including: greater program integration with the new Rebecca and John Moores UCSD Cancer Center;increased cancer relevance of our faculty;doubling of our predoctoral pool;proposed change to increase the proportion of postdoctoral trainees;definition of research focus groups;endorsements from key administrative leaders;and improved mechanisms to build program cohesion.